Experimental autoimmune encephalomyelitis (EAE) was induced in the susceptible SJL/J mouse strain by immunization with the myelin basic protein. Lymph node cells from these immunized mice were inoculated into nanve SJL/J mice, which induces an EAE condition that involves cycles of relapse and remission. Relapse was associated with increased IFN-g. In contrast, remission cycles were immediately preceded by peak levels of indoleamine 2,3-dioxygenase (IDO) detected in neurons but not in other tissue. IDO is an enzyme that catabolizes tryptophan, which is required for T lymphocyte survival. These results raises the possibility that IDO contributes to the remission phases of EAE (and possibly MS) by destroying specific T cells residing in nervous tissue that contribute to this autoimmune condition. Our preliminary data using longitudinal, cryopreserved blood samples from remitting and relapsing patients with multiple sclerosis suggest that IFN-g is indreased during or preceeding relapse and that IDO is aupregulated during or preceeding the remission phases. These findings may shed light on the regulatory aspects of this autoimmune disease.